1. Field of the Invention
The present disclosure relates to a composition for preventing or treating asthma, the composition containing styraxlignolide A or an aglycone thereof as an active ingredient.
2. Description of the Related Art
Allergic diseases of which incidence rate is globally on the increase include anaphylaxis, allergic rhinitis, asthma, atopic dermatitis and urticaria (Wuthrich B. Int. Arch. Allergy Appl. Immunol., 90, pp 3-10, 1989).
Among these allergic diseases, asthma is a chronic inflammatory respiratory disease, from which about 3 million people in Republic of Korea are estimated to suffer, and which is characterized by symptoms of cough, wheezing, that is a high-pitched whistling sound during breathing, shortness of breath, chest tightness, and the number of patients has lately increased suddenly due to intensified atmospheric pollution, and westernization of dietary life. Asthma is the most common disease in the more developed countries such as the United States, the United Kingdom, and it is estimated that 20-30% of the total population are patients. In Republic of Korea, 16% of primary school children, about 5% of adults, and total 4 million or more are estimated to be patients, and asthma is a common disease, which can be seen in all age groups from early childhood or childhood to the elderly and 10% of total population suffer from. For the cause, atopic constitution which causes allergy in a family was identified to be a basic factor, and airway hyperresponsiveness, eosinophil inflammation in airway, and accentuation of Th2 immune response are reported to be basic factors. Due to asthma, difficulty in breathing, severe coughs, and wheezing (a high-pitched whistling sound during breathing) occur, and according to WHO's special report published in 2000, 150 million patients suffer from asthma worldwide, and 180,000 die of bronchial asthma each year. Furthermore, WHO's special report commented that the disease prevalence rate and severity are continuously on an increasing trend, and medical and social costs due to asthma surpass those for pulmonary tuberculosis and AIDS combined.
In case of Republic of Korea, the prevalence rate of childhood asthma was only 3-4% in early 1980s, and increased 2-fold or more. According to ‘ISAAC (International Study of Asthma and Allergy in Childhood)’ published in 1998, the prevalence rate of childhood asthma was 13.3% in Korean children aged 6-7-years, and 7.7% in children aged 13-14 years. Taken those children as a whole, ten out of one hundred children suffer from asthma, and five, 50% of them, would suffer from asthma for terms of life. Not only the prevalent rate but also severity of the disease worsens the seriousness of the problem.
Asthma is generally recognized as chronic inflammatory disease which is caused by the migration and infiltration of inflammatory cells proliferated, differentiated, and activated by interleukin-4, 5, and 13 generated by TH2 immunocytes into and around the airway (Elias J A, et al., J. Clin. Invest., 111, pp 291-297, 2003). At this time, the activated inflammatory cells such as eosinophils, mast cells and alveolar macrophages secret various inflammation mediators (cysteinyl leukotriene, prostaglandin, etc), which play a critical role in bronchoconstriction (Maggi E., Immunotechnology, 3, pp 233-244, 1998; Pawankar R., Curr. Opin. Allergy Clin. Immunol., 1, pp 3-6, 2001; Barnes P J, et al., Pharmacol Rev., 50, pp 515-596, 1998).
Productions of cytokines involved in the activation of inflammatory cells such as IL-4, IL-5, and IL-13, and immunoglobulin E, as well as biosynthesis of cysteinyl leukotriene secreted from inflammatory cells such as eosinophils mediated by the cytokines and immunoglobulin E are major causes of inflammation and allergic reaction and asthma caused by such inflammation and allergic reaction. Therefore, studies are actively undergoing to develop drugs to inhibit their productions.
Currently, various therapeutic agents are commercially available, but a lot of therapeutic agents have side effects and require caution when using. Inhalation corticosteroid preparations are still the most important therapeutic agent, and exhibit excellent effects, but they are known to result in adrenal suppression, bone density decrease, failure to thrive, ocular and skin complications, etc. when using for long time in proportion to doses and use time. In addition, there is a report that corticosteroids can rather increase collagen synthesis (Warshmana G S, et al., Am J Physiol 274, 499-507, 1998). Thus, in spite of corticosteroid treatment for several years for patients with chronic persistent asthma, there are few patients with asthma whose hyperresponsiveness is normalized. Long-term administration of beta-2 agonists are known not to inhibit airway remodeling (Jeffery P K, et al., Am Rev Respir Dis 145: 890-0, 1992), and it has been warned that long-acting beta-2 agonists such as salmeterol and formeterol prevent asthmatic attack, and rather can result in deaths in patients with asthma. These various adverse effects have been reported, but have been continuously prescribed under the conclusion that their effects of alleviating asthmatic symptoms are larger than risks of adverse effects. When the growth quotient of children asthmatic patients who are sensitive to adverse effects was measured, the growth quotient of children asthmatic patients who took oral leukotriene antagonist (montelukast) was shown to be superior to that of children asthmatic patients who used inhalation corticosteroid up to 1 cm per year (Garcia Garcia M L, et al., Pediatrics 116(2): 360-9, 2005). If asthma is not controlled in the growing period, the growth of overall body as well as lung can be inhibited, and thus, maintaining normal lung function through continued treatment is essential for growth, but it was identified that nothing is more important than to use a safe drug for continued treatment and care for respiratory inflammation. Thus, when choosing therapeutic agents, adverse effects as well as effects of alleviating asthma should be considered carefully. Leukotriene antagonists are known to have a low frequency of adverse effects, and are newly used for preventing asthma and continued treatment. However, their effects of alleviating asthma are weaker than other drugs, and they show remarkable effects only in one-third of patients. Therefore, development of novel therapeutic agents for asthma which are nontoxic and safe, and can prevent drug resistance is required.
Styrax japonica is a tree in the Styracaceae family, Ericales, and is native to Korea, China, and Japan, and is a deciduous tall tree. It grows up to approximately 10 to 15 m tall, and is very resistant to cold and pollution. The bark is dark brown, and leaves are alternate, egg-shaped or long-oval shape, and pointed at the end. Fruits are drupaceous, ripen in September, oval shape, and when ripe, the skin splits irregularly. For components of Styrax japonica, about 10% of egosaponin is in the fruit skin, various kinds of glycerides, fatty oil, and egonol are in seeds, and saponin is in flowers. Styrax japonica is called as Maemadeung, Jedongwa, and is used medicinally. In oriental medicine, Styrax japonica is used for getting rid of intestinal worms, killing insects, discharge of irritable phlegm, laryngitis, preservatives, etc., and is known to have efficacies in cyanidation, airing and dehumidification, and treat afterpain, Atong (toothache), Chitong (toothache), arthritis due to wind-dampness, melagia, etc.
Thus, the present inventors have been focused on herb medicine in the light of adverse effects and safety in a living body, and above all, the present inventors have performed research to develop therapeutic agents for asthma, which are capable of being used for long-term treatment and have an inhibitory effect on airway remodeling, identified that styraxlignolide A isolated from Styrax japonica or its aglycone homoegonol have excellent inhibiting effects on airway hyperresponsiveness, endobronchial infiltration of inflammatory cells, and progress of airway remodeling (bronchial epithelial cell thickening, mucous secretory cell hyperplasia, progress of fibrosis) in an asthma-induced model, compared to the current widely used drugs for asthma, dexamethasone or montelukast, and proved that styraxlignolide A or homoegonol can be used as an active ingredient of a compound for preventing or treating asthma, thereby leading to completion of the present invention.